Pharmacokinetic Exposures Associated With Oral Administration of Sorafenib in Dogs With Spontaneous Tumors
Sorafenib is a multi-kinase small molecule inhibitor that targets serine/threonine and tyrosine kinases including the RAF kinase family, VEGFR-2, and PDGFR. The aim of this study was to evaluate the systemic pharmacokinetics of a previously defined tolerable oral dose of sorafenib in tumor-bearing d...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-05-01
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| Series: | Frontiers in Veterinary Science |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fvets.2022.888483/full |
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| author | Jacob R. Cawley Jacob R. Cawley Samuel D. Stewart Samuel D. Stewart Jonathan Paul Mochel Sridhar Veluvolu Chand Khanna Chand Khanna Joelle M. Fenger Joelle M. Fenger |
| author_facet | Jacob R. Cawley Jacob R. Cawley Samuel D. Stewart Samuel D. Stewart Jonathan Paul Mochel Sridhar Veluvolu Chand Khanna Chand Khanna Joelle M. Fenger Joelle M. Fenger |
| author_sort | Jacob R. Cawley |
| collection | DOAJ |
| description | Sorafenib is a multi-kinase small molecule inhibitor that targets serine/threonine and tyrosine kinases including the RAF kinase family, VEGFR-2, and PDGFR. The aim of this study was to evaluate the systemic pharmacokinetics of a previously defined tolerable oral dose of sorafenib in tumor-bearing dogs. Six client-owned dogs with a cytologic or histologic diagnosis of cancer were enrolled in this open-label, tolerability study. Dogs were administered sorafenib at an intended dose of 3 mg/kg and serum samples were obtained for analysis of sorafenib serum concentrations at 0, 1, 2, 6, 12, 24, 48, 72, 96, and 168 h post-drug administration. Median time to peak serum sorafenib concentration occurred at 4 h (range 2–12 h) resulting in an average serum concentration of 54.9 ± 33.5 ng/mL (118.2 ± 72.1 nM). Mean sorafenib levels declined by over 70% relative to peak serum concentrations by 24 h in all dogs, suggesting the value of at least twice daily administration. Doses of 3 mg/kg were well-tolerated and no patients in the study experienced adverse events that were attributable to sorafenib. Future trials in dogs with cancer are recommended at this dosing schedule to assess the effect of sorafenib administration on anti-tumor efficacy signals and relevant pharmacodynamic target modulation in vivo. |
| first_indexed | 2024-04-12T14:57:55Z |
| format | Article |
| id | doaj.art-52d756177d0d4505bdab09aa7451747f |
| institution | Directory Open Access Journal |
| issn | 2297-1769 |
| language | English |
| last_indexed | 2024-04-12T14:57:55Z |
| publishDate | 2022-05-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Veterinary Science |
| spelling | doaj.art-52d756177d0d4505bdab09aa7451747f2022-12-22T03:28:11ZengFrontiers Media S.A.Frontiers in Veterinary Science2297-17692022-05-01910.3389/fvets.2022.888483888483Pharmacokinetic Exposures Associated With Oral Administration of Sorafenib in Dogs With Spontaneous TumorsJacob R. Cawley0Jacob R. Cawley1Samuel D. Stewart2Samuel D. Stewart3Jonathan Paul Mochel4Sridhar Veluvolu5Chand Khanna6Chand Khanna7Joelle M. Fenger8Joelle M. Fenger9Ethos Veterinary Health, Woburn, MA, United StatesEthos Discovery (501c3), San Diego, CA, United StatesEthos Veterinary Health, Woburn, MA, United StatesEthos Discovery (501c3), San Diego, CA, United StatesSMART Pharmacology, Department of Biomedical Sciences, College of Veterinary Medicine, Iowa State University, Ames, IA, United StatesWilliam R. Pritchard Veterinary Medical Teaching Hospital, School of Veterinary Medicine, University of California, Davis, Davis, CA, United StatesEthos Veterinary Health, Woburn, MA, United StatesEthos Discovery (501c3), San Diego, CA, United StatesEthos Veterinary Health, Woburn, MA, United StatesEthos Discovery (501c3), San Diego, CA, United StatesSorafenib is a multi-kinase small molecule inhibitor that targets serine/threonine and tyrosine kinases including the RAF kinase family, VEGFR-2, and PDGFR. The aim of this study was to evaluate the systemic pharmacokinetics of a previously defined tolerable oral dose of sorafenib in tumor-bearing dogs. Six client-owned dogs with a cytologic or histologic diagnosis of cancer were enrolled in this open-label, tolerability study. Dogs were administered sorafenib at an intended dose of 3 mg/kg and serum samples were obtained for analysis of sorafenib serum concentrations at 0, 1, 2, 6, 12, 24, 48, 72, 96, and 168 h post-drug administration. Median time to peak serum sorafenib concentration occurred at 4 h (range 2–12 h) resulting in an average serum concentration of 54.9 ± 33.5 ng/mL (118.2 ± 72.1 nM). Mean sorafenib levels declined by over 70% relative to peak serum concentrations by 24 h in all dogs, suggesting the value of at least twice daily administration. Doses of 3 mg/kg were well-tolerated and no patients in the study experienced adverse events that were attributable to sorafenib. Future trials in dogs with cancer are recommended at this dosing schedule to assess the effect of sorafenib administration on anti-tumor efficacy signals and relevant pharmacodynamic target modulation in vivo.https://www.frontiersin.org/articles/10.3389/fvets.2022.888483/fullsorafenibmulti-target kinase inhibitorspharmacokineticsdogcancer |
| spellingShingle | Jacob R. Cawley Jacob R. Cawley Samuel D. Stewart Samuel D. Stewart Jonathan Paul Mochel Sridhar Veluvolu Chand Khanna Chand Khanna Joelle M. Fenger Joelle M. Fenger Pharmacokinetic Exposures Associated With Oral Administration of Sorafenib in Dogs With Spontaneous Tumors Frontiers in Veterinary Science sorafenib multi-target kinase inhibitors pharmacokinetics dog cancer |
| title | Pharmacokinetic Exposures Associated With Oral Administration of Sorafenib in Dogs With Spontaneous Tumors |
| title_full | Pharmacokinetic Exposures Associated With Oral Administration of Sorafenib in Dogs With Spontaneous Tumors |
| title_fullStr | Pharmacokinetic Exposures Associated With Oral Administration of Sorafenib in Dogs With Spontaneous Tumors |
| title_full_unstemmed | Pharmacokinetic Exposures Associated With Oral Administration of Sorafenib in Dogs With Spontaneous Tumors |
| title_short | Pharmacokinetic Exposures Associated With Oral Administration of Sorafenib in Dogs With Spontaneous Tumors |
| title_sort | pharmacokinetic exposures associated with oral administration of sorafenib in dogs with spontaneous tumors |
| topic | sorafenib multi-target kinase inhibitors pharmacokinetics dog cancer |
| url | https://www.frontiersin.org/articles/10.3389/fvets.2022.888483/full |
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